249922-60-9Relevant academic research and scientific papers
Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: Scope and DFT study
Katayev, Dmitry,Larionov, Evgeny,Nakanishi, Masafumi,Besnard, Cline,Kündig, E. Peter
supporting information, p. 15021 - 15030 (2015/02/19)
Two bulky, chiral, monodentate N-heterocyclic carbene ligands were applied to palladium-catalyzed asymmetric C-H arylation to incorporate C(sp3)-H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans-2,3- substituted indolines. Although this CAr-Calkyl coupling requires high temperatures (140-160°C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The C-H activation at a tertiary center was realized only in the case of a cyclopropyl group. No C-H activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine C-H activation is used to rationalize experimentally observed regio- and enantioselectivities.
Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors
Wilson, Stuart C.,Atrash, Butrus,Barlow, Clare,Eccles, Susan,Fischer, Peter M.,Hayes, Angela,Kelland, Lloyd,Jackson, Wayne,Jarman, Michael,Mirza, Amin,Moreno, Javier,Nutley, Bernard P.,Raynaud, Florence I.,Sheldrake, Peter,Walton, Mike,Westwood, Robert,Whittaker, Steven,Workman, Paul,McDonald, Edward
experimental part, p. 6949 - 6965 (2012/01/14)
The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound αSβR-21 inhibits CDK2/cyclin E with IC50 = 30 nM, CDK7-cyclin H with IC50 = 1.3 μM, and CDK9-cyclinT with IC50 = 0.11 μM; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI50 = 0.7 μM; and shows antitumour activity when dosed p.o. at 50 mg/kg to mice bearing HCT116 solid human tumour xenografts.
COMBINATION OF A PURINE-BASED CDK INHIBITOR WITH A TYROSINE KINASE INHIBITOR AND USE THEREOF IN THE TREATMENT OF PROLIFERATIVE DISORDERS
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Page/Page column 38-39, (2008/12/04)
The present invention relates to combination comprising (i) an ErbB inhibitor; and (ii) a CDK inhibitor, or a pharmaceutically acceptable salt thereof, selected from: (a) roscovitine; (b) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-
4,5-Dialkylsubstituted 2-imino-1,3-thiazolidine derivatives as potent inducible nitric oxide synthase inhibitors
Ueda, Shigeo,Terauchi, Hideo,Yano, Akihiro,Matsumoto, Masashi,Kubo, Taeko,Kyoya, Yoko,Suzuki, Kenji,Ido, Motoharu,Kawasaki, Motoji
, p. 4101 - 4116 (2007/10/03)
In the course of our search for selective iNOS inhibitors, we have previously reported that 2-imino-1,3-oxazolidine derivatives (1) and 2-aminothiazole derivatives (2) are selective iNOS inhibitors. In order to find more potent iNOS inhibitors, we focused
Stereoselective deprotonation of chiral and achiral 2-aminoalkyl carbamates: Synthesis of optically active β-amino alcohols via 1-oxy- substituted alkyllithium intermediates
Schwerdtfeger, J?rg,Kolczewski, Sabine,Weber, Berthold,Fr?hlich, Roland,Hoppe, Dieter
, p. 1573 - 1592 (2007/10/03)
A facile protocol for the electrophilic C-substitution (methylation, acylation, α-hydroxyalkylation, and carboxylation) of several 2-(N,N- dibenzylamino)alkan-1-ols via the carbamates 10 is reported. The stereochemistry of the lithiation is greatly influenced by the complexing diamine. The substrate-directed selection between the diastereotopic a-pro-R and pro-S protons in the TMEDA-assisted deprotonation is largely shifted towards pro-S-selectivity in the presence of (-)-sparteine (4). Each of both diastereomeric series is readily accessible in several cases.
